Penicillin Non-susceptible Pneumococci Research Articles

Prevalence, capsular types, antimicrobial resistance and risk factors associated with pneumococcal carriage among children after long-term 10-valent pneumococcal conjugate vaccine use in Brazil.

The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced for childhood vaccination in Brazil's National Immunization Program in 2010. After nine years of PCV10 use, we investigated the carriage prevalence, capsular types, antimicrobial resistance and risk factors among children living in Niterói city, RJ, Brazil. Between September and December 2019, we conducted a cross-sectional study and recruited children under 6years of age. Antimicrobial susceptibility was evaluated by the disk-diffusion method and MICs to beta-lactams and macrolides were determined by E-test®. Capsular types were deduced by multiplex PCR. Logistic regression was used to predict risk factors for pneumococcal carriage. Seventy-five (17.4%) of the 430 children were pneumococcal carriers. The most frequent capsular types were 6C/D (14.7%), 11A/D (13.3%), and 23B (9.3%). PCV10 serotypes represented 5.3%. All isolates were susceptible to levofloxacin, linezolid, rifampicin, and vancomycin. Penicillin non-susceptible pneumococci (PNSP) made up 37.3%, with penicillin and ceftriaxone MICs ranging from 0.12 to 4.0μg/ml and 0.064-4.0μg/ml, respectively. Of the 19 (25.3%) erythromycin-resistant (ERY-R) isolates (macrolide MICs of 6 to>256μg/ml), most had the cMLSB phenotype (84.2%) and carried the erm(B) gene (73.7%). We detected 17 (22.6%) multidrug-resistant (MDR) isolates, strongly associated with serotype 6C/D. Presence of any symptoms, chronic diseases, childcare center attendance, living with young siblings, slum residence, and unstable income were predictors of pneumococcal carriage. Long-term universal childhood use of PCV10 has nearly eliminated carriage with PCV10 serotypes, but the high frequency of MDR isolates, especially associated with serotype 6C/D, remains a concern. Replacing PCV10 with PCV13 should reduce the proportion of ERY-R isolates and PNSP by at least 14% and 18%, respectively.

Carriage prevalence, serotype distribution, antimicrobial resistance, pspA typing and pilus islets of Streptococcus pneumoniae isolated from adults living in a Brazilian urban slum.

For Brazilian adults, pneumococcal vaccines have been usually taken only by those who are at higher risk for development of pneumococcal diseases. Since populations from lower socioeconomic status are at high risk of acquiring pneumococcal infections, we investigated the carriage prevalence, colonization risk factors, capsular and surface protein types, and antimicrobial resistance among pneumococcal isolates recovered from adults living in a Brazilian urban slum. Between September-December 2016, we conducted a cross-sectional study among individuals aged≥18years who attended a public primary clinic in Niterói/RJ, Brazil. Pneumococci were isolated by culture on sheep blood agar plates with and without gentamicin. Antimicrobial susceptibility was determined for all isolates. We used PCR to determine capsular types, PspA families (Fam) and pilus islets (PI). Of 385 adults, 32 (8.3%) were pneumococcal carriers. Three carriers had two different pneumococci, totaling 35 isolates. After multivariate analysis, smoking, previous hospitalization, alcohol consumption and co-habitation with children aged<6years increased the odds of pneumococcal carriage, but antibiotic use in the previous 2weeks was found to be a protective factor. Fourteen different serogroups/serotypes were detected and the prevalent ones were 9N/L, 10A, 15B/C and 35F/47F (n=3; 8.6% each). Non-typeable (NT) isolates made up 31.4%. All isolates were susceptible to chloramphenicol, levofloxacin and vancomycin. We found eight (22.9%) penicillin non-susceptible pneumococci (PNSP) with minimum inhibitory concentrations (MICs) of 0.38-1.5μg/mL. The two (5.7%) erythromycin-resistant isolates had MIC>256μg/mL, cMLSB phenotype and the erm(B) gene. Twelve (34.3%) and 17 (48.6%) isolates had PspA Fam1 and Fam2, respectively. Three (8.6%) isolates had genes for pilitwo PI-1 and one PI-2. We detected a low frequency of pneumococcal carriage among the adult population, but a high diversity of serotypes. Frequencies of PNSP and NT isolates resistant to antimicrobial agents are concerning.

Streptococcus pneumoniae vaccination strategies and its expected impact on penicillin non-susceptibility in children under the age of five: Let's recap!

The impact of pneumococcal conjugate vaccines (PCVs) on invasive pneumococcal disease (IPD) burden has been extensively studied in children aged<5 years; however, a pooled estimation of the effect of PCVs on penicillin non-susceptible pneumococci (PNSP) has not yet been performed. We aimed to identify whether the introduction of PCV-10 and PCV-13 had led to the decrease of the overall PNSP rate in children < 5 years. We conducted a systematic review of published surveillance studies reporting the rate of PNSP rates in children < 5 in countries where PCV10/13 were introduced. The overall observed trend onwards the introduction of PCV-10 and PCV-13 is a decrease in PNSP among children < 5 years in surveillance sites located in PCV-13 countries. We identified an increase of PNSP rates (serotype 19A) in PCV-10 settings. Resistant NVT strains are emerging in IPD in children < 5 years mainly serotypes 24F, 15A, 11A and 33F along with serotype 19A in PCV-10 settings. Continuous surveillance is necessary in IPD in children under five to monitor the long-term effect of PCV-10 and PCV-13 on penicillin resistance trends.

Serotype distribution and antimicrobial resistance of Streptococcus pneumoniae among children with acute otitis media in Marrakech, Morocco.

Background and Objectives:Streptococcus pneumonia (S. pneumoniae) is one of the most frequent pathogens leading to a variety of clinical manifestations. The effects of S. pneumoniae carriage on acute otitis media (AOM) are poorly studied. The study aimed to assess the serotype’s distribution and antimicrobial susceptibility in children with AOM after the implementation of the pneumococcal conjugate vaccine (PCV) in Morocco.Materials and Methods:We conducted a prospective study of AOM children aged 6 to 36 months who visited pediatric centers in Marrakesh between January to June 2018. Parents were asked to complete a questionnaire and a swab was collected from each child. The S. pneumoniae strains were further identified (Hemolysis, optochin sensitivity, and agglutination test), serogrouped (IMMULEX PNEUMOTEST agglutination test), serotyped (Real time PCR) and tested for antimicrobial susceptibility.Results:The S. pneumoniae carriage rate was 49.7% (87/175). As estimated, non-vaccine serotypes (NVT) were most prevalent (51/63; 81%). The most frequent serotypes were 6C/6D (12.7%), 10 (9.5%), and 19B/19C (9.5%). The S. pneumoniae strains that were isolated showed a diminished susceptibility to penicillin G with a rate of 27.5%. Penicillin non-susceptible pneumococci (PNSP) was mostly associated with NVT. More than 90% of S. pneumoniae isolates were susceptible to chloramphenicol (97.5%), clindamycin (97.5%), erythromycin (97.5%), levofloxacin (97.5%), pristinamycin (97.5%), gentamicin (92.5%), and teicoplanin (92.5%).Conclusion:Important nasopharyngeal carriage prevalence was reported among children with AOM. The study showed that new NVT are emerging, including 6C/6D and 10. Furthermore, susceptibility was significantly higher against all antibiotics tested except for penicillin G and amoxicillin.

Characterization of Blood-isolated, Penicillin-Nonsusceptible Streptococcus pneumoniae From Children Between 2014 and 2018 in Bojnurd, Iran

Background: Streptococcus pneumoniae is one of the common bacterial pathogens in pediatrics. In this study, we performed antimicrobial susceptibility testing, serotyping, and molecular typing of blood-isolated strains of pneumococci in Bojnurd. Objectives: In the current study, blood-isolated, penicillin-nonsusceptible S. pneumoniae strains were subjected to antimicrobial susceptibility testing and typing of capsular polysaccharides using the quelling reaction and PCR method, as well as genotyping using the Multi Locus Sequence Typing (MLST) method. Methods: In this study, 51 S. pneumoniae strains were isolated from blood samples of children less than five-years-old in 2014 - 2018. Antibiogram was performed using the Kirby-Bauer method. All of the isolates were serotyped by the Quelling reaction and PCR. The MLST method was applied to determine the molecular types. Results: Our study revealed that the most common serotypes of blood-isolated pneumococci were 19A, 6A/B, 1, 23F, 19F, 14, 15B/C, and 15A, and the common serotypes in Penicillin-nonsusceptible pneumococci (PNSP) isolates were 19F, 19A, 23F, 14, and finally 15A, 6A/B, 1, and 15B/C. The MLST analysis of PNSP isolates revealed that three highly resistant isolates with MIC ≥ 16 belonged to Sweden15A-25-19A (ST63), Taiwan19F-14-1 (ST236), and Taiwan19F-14 (ST236) clones. Conclusions: Regarding the common serotypes in this study, it seems that PCV-13 is a suitable choice for vaccination in this area. We also observed a high prevalence of PNSP and multi-drug resistant (MDR) strains between 2014 and 2018. It seems that the Taiwan19F-14 clone and its related STs played an essential role in the diffusion of antibiotic-resistant S. pneumoniae isolates in Bojnurd.

Reduction of antimicrobial resistant pneumococci seven years after introduction of pneumococcal vaccine in Iceland

Penicillin non-susceptible (PNSP) and multi-resistant pneumococci have been prevalent in Iceland since early nineties, mainly causing problems in treatment of acute otitis media. The 10-valent protein conjugated pneumococcal vaccine (PHiD-CV) was introduced into the childhood vaccination program in 2011. The aim of the study was to investigate the changes in antimicrobial susceptibility and serotype distribution of penicillin non-susceptible pneumococci (PNSP) in Iceland 2011-2017. All pneumococcal isolates identified at the Landspítali University Hospital in 2011-2017, excluding isolates from the nasopharynx and throat were studied. Susceptibility testing was done according to the EUCAST guidelines using disk diffusion with chloramphenicol, erythromycin, clindamycin, tetracycline, trimethoprim/sulfamethoxazole and oxacillin for PNSP screening. Penicillin and ceftriaxone minimum inhibitory concentrations (MIC) were measured for oxacillin resistant isolates using the E-test. Serotyping was done using latex agglutination and/or multiplex PCR. The total number of pneumococcal isolates that met the study criteria was 1,706, of which 516 (30.2%) were PNSP, and declining with time. PNSP isolates of PHiD-CV vaccine serotypes (VT) were 362/516 (70.2%) declining with time, 132/143 (92.3%) in 2011 and 17/54 (31.5%) in 2017. PNSP were most commonly of serotype 19F, 317/516 isolates declining with time, 124/143 in 2011 and 15/54 in 2017. Their number decreased in all age groups, but mainly in the youngest children. PNSP isolates of non PHiD-CV vaccine serotypes (NVT) were 154/516, increasing with time, 11/14, in 2011 and 37/54 in 2017. The most common emerging NVTs in 2011 and 2017 were 6C, 1/143 and 10/54 respectively. PNSP of VTs have virtually disappeared from children with pneumococcal diseases after the initiation of pneumococcal vaccination in Iceland and a clear herd effect was observed. This was mainly driven by a decrease of PNSP isolates belonging to a serotype 19F multi-resistant lineage. However, emerging multi-resistant NVT isolates are of concern.

Direct effect of the 13-valent pneumococcal conjugate vaccine use on pneumococcal colonization among children in Brazil

BackgroundThe 13-valent pneumococcal conjugate vaccine (PCV13) has been commercially available in Brazil since 2010. We investigated the carriage prevalence, capsular types, and antimicrobial resistance among pneumococci isolated from children immunized with PCV13 in Brazil. MethodsWe analyzed 500 children < 6 years old attending public (n = 270) and private (n = 230) clinics in Niterói/RJ, Brazil, in 2014. We determined the antimicrobial susceptibility and capsular types for all isolates. ResultsThirty-eight (7.6%) of 500 children had received at least one PCV13 dose. Since only two (0.7%) of 270 children at the public clinic were vaccinated with PCV13, major analyses focused on 36 (15.7%) of 230 children attending private clinics. Nine (25%) of 36 children were pneumococcal carriers. Characteristics associated with carriage were age ≥ 2 years, cough/expectoration, and childcare center attendance (p ≤ 0.01). The capsular types found were 15B/C (n = 2), 6C, 11A/D, 16F, 23A, and 23F. Two isolates were non-typeable (NT). Three (33.3%) isolates were multidrug resistant. We found four (44.4%) penicillin non-susceptible pneumococci, with penicillin and ceftriaxone MICs ranging from 0.12 to 4.0 µg/ml and 0.023–0.5 µg/ml, respectively. We also detected two (22.2%) erythromycin-resistant isolates (MICs of 3.0 and 256 µg/ml). ConclusionsColonization with PCV13 serotype was rare among the vaccinated children. Increasing PCV13 coverage might help reduce the frequency of major serotypes currently associated with invasive pneumococcal diseases in Brazil, such as 3 and 19A. The isolation of multidrug-resistant serotype 6C and NT isolates in carriage, however, requires close monitoring.

Pneumococcal susceptibility to antibiotics in carriage: a 17 year time series analysis of the adaptive evolution of non-vaccine emerging serotypes to a new selective pressure environment.

Pneumococcal conjugate vaccine (PCV) implementations led to major changes in serotype distribution and antibiotic resistance in carriage, accompanied by changes in antibiotic consumption. To assess the dynamic patterns of antimicrobial non-susceptibility across non-PCV13 serotypes following PCV implementations. We conducted a quasi-experimental interrupted time series analysis based on a 17 year French nationwide prospective cohort. From 2001 to 2018, 121 paediatricians obtained nasopharyngeal swabs from children with acute otitis media who were aged 6 months to 2 years. The main outcome was the rate of penicillin-non-susceptible pneumococci (PNSP), analysed by segmented regression. We enrolled 10 204 children. After PCV13 implementation, the PNSP rate decreased (-0.5% per month; 95% CI -0.9 to -0.1), then, after 2014, the rate slightly increased (+0.7% per month; 95% CI +0.2 to +1.2). Global antibiotic use within the previous 3 months decreased over the study period (-22.2%; 95% CI -33.0 to -11.3), but aminopenicillin use remained high. Among the main non-PCV13 serotypes, four dynamic patterns of penicillin susceptibility evolution were observed, including unexpected patterns of serotypes emerging while remaining or even becoming penicillin susceptible. In contrast to PNSP strains, for these latter patterns, the rate of co-colonization with Haemophilus influenzae increased concomitant with their emergence. In a context of continuing high antibiotic selective pressure, a progressive increase in PNSP rate was observed after 2014. However, we highlighted an unexpected variability in dynamic patterns of penicillin susceptibility among emerging non-PCV13 serotypes. Antibiotic resistance may not be the only adaptive mechanism to antimicrobial selective pressure, and co-colonization with H. influenzae may be involved.

The association of pili with the emergence and replacement of the major antibiotic resistant pneumococcal clones.

The aim of this study was to evaluate the presence of pilus islet 1 (PI-1) and to determine its clade type in pneumococcal isolates with reduced susceptibility to penicillin (penicillin non-susceptible pneumococci - PNSP) and/or resistant to macrolides isolated prior to and after the introduction of pneumococcal conjugate vaccines (PCVs) in the Czech Republic. Clinical isolates of serotypes 9V (n=68) and 19A (n=89) were examined. Isolates were characterised by multilocus sequence typing (MLST). The presence of PI-1 was determined by screening for the sortase B, C, and D genes located within PI-1. In the presence of PI-1 pilus, clade types were classified by PCR. In the pre-PCV period (2000-2007), the prevalence of PNSP was 3.9% and 2.7% of isolates were resistant to erythromycin. During 2012-2015 (post-PCV period), the rates of PNSP remained stable (3.6%), but resistance to erythromycin increased to 8.3%. While in 2000-2007, resistance to antibiotics was associated mainly with serotype 9V, in 2012-2015, it was replaced by serotype 19A. PI-1 positive isolates were seen in both serotypes. All isolates (68) of serotype 9V belonged to the Spain9V-3 (CC156) clone and carried PI-1 of clade type I while 96.5% (56/58) of isolates of 19A serotype belonged to the Netherlands15B-37 (CC199) clone and carried PI-1 of clade type II. Both major antibiotic resistant clones carried PI-1, although they differ in the clade type. Thus the role of PI-1 should be evaluated in further studies and potentially considered in the spread of antibiotic resistant clones.

Impact of 10-Valent Pneumococcal Conjugate Vaccine Introduction on Pneumococcal Carriage and Antibiotic Susceptibility Patterns Among Children Aged

Background.Kenya introduced 10-valent pneumococcal conjugate vaccine (PCV10) among children <1 year in 2011 with catch-up vaccination among children 1–4 years in some areas. We assessed changes in pneumococcal carriage and antibiotic susceptibility patterns in children <5 years and adults.Methods.During 2009–2013, we performed annual cross-sectional pneumococcal carriage surveys in 2 sites: Kibera (children <5 years) and Lwak (children <5 years, adults). Only Lwak had catch-up vaccination. Nasopharyngeal and oropharyngeal (adults only) swabs underwent culture for pneumococci; isolates were serotyped. Antibiotic susceptibility testing was performed on isolates from 2009 and 2013; penicillin nonsusceptible pneumococci (PNSP) was defined as penicillin-intermediate or -resistant. Changes in pneumococcal carriage by age (<1 year, 1–4 years, adults), site, and human immunodeficiency virus (HIV) status (adults only) were calculated using modified Poisson regression, with 2009–2010 as baseline.Results.We enrolled 2962 children (2073 in Kibera, 889 in Lwak) and 2590 adults (2028 HIV+, 562 HIV−). In 2013, PCV10-type carriage was 10.3% (Lwak) to 14.6% (Kibera) in children <1 year and 13.8% (Lwak) to 18.7% (Kibera) in children 1–4 years. This represents reductions of 60% and 63% among children <1 year and 52% and 60% among children 1–4 years in Kibera and Lwak, respectively. In adults, PCV10-type carriage decreased from 12.9% to 2.8% (HIV+) and from 11.8% to 0.7% (HIV−). Approximately 80% of isolates were PNSP, both in 2009 and 2013.Conclusions.PCV10-type carriage declined in children <5 years and adults post–PCV10 introduction. However, PCV10-type and PNSP carriage persisted in children regardless of catch-up vaccination.

Evolution of Penicillin Non-susceptibility Among Streptococcus pneumoniae Isolates Recovered From Asymptomatic Carriage and Invasive Disease Over 25 years in Brazil, 1990-2014.

Streptococcus pneumoniae is a major cause of community-acquired pneumonia and meningitis, and it is also found as a commensal, colonizing the human upper respiratory tract of a portion of the human population. Its polysaccharide capsule allows the recognition of more than 90 capsular types and represents the target of the currently available pneumococcal conjugate vaccines (PCVs), such as the 10-valent (PCV10) and the 13-valent (PCV13). Penicillin non-susceptible pneumococci (PNSP) have been listed as one of the current major antimicrobial-resistant pathogen threats. In Brazil, the emergence of PNSP was initially detected in the mid 1990s and PCV10 has been part of the National Immunization Program since 2010. Here, we investigated the distribution of capsular types and penicillin susceptibility profiles of 783 pneumococcal strains isolated in Brazil between 1990 and 2014 to assess the evolution of penicillin non-susceptibility among pneumococci associated with asymptomatic carriage and invasive pneumococcal disease (IPD). The most common serotypes among carriage isolates were 19F, 6B, 6C, 23F, and 14. Among IPD isolates, the most frequent types were 14, 3, 6B, 5, 19F, and 4. We detected 21 types exclusively associated with IPD isolates, whereas non-typeable (NT) isolates were only detected in carriage. Nearly half of the isolates belonged to PCV10 serotypes, which remarkably decreased in occurrence (by nearly 50%) after PCV10 introduction (2011–2014), while non-PCV10 serotypes increased. PNSP frequency and levels were much higher among carriage isolates, but PNSP belonging to PCV10 serotypes were more common in IPD. While the occurrence of PNSP has decreased significantly among IPD isolates since 2011, it kept increasing among carriage strains. Such a difference can be attributed to the serotypes that emerged in each clinical source after PCV10 usage. PNSP with multidrug resistance profiles that emerged within carriage isolates comprised mostly serotypes 6C and 35B, as well as NT isolates. In turn, penicillin-susceptible capsular types 3, 20, and 8 have risen among IPD. Overall, our results reinforce the relevance of PNSP surveillance over a long period of time to better understand the dynamics of antimicrobial resistance in response to PCV introduction and may also contribute to improve control measures toward drug-resistant pneumococci.

1445. Impact of 10-Valent Pneumococcal Conjugate Vaccine Introduction on Pneumococcal Carriage and Antibiotic Susceptibility Patterns Among Children Aged &lt;5 Years and Adults with HIV Infection, Kenya 2009–2013

BackgroundKenya introduced 10-valent pneumococcal conjugate vaccine (PCV10) in 2011 (three doses at ages 6, 10, and 14 weeks). Impact of PCV10 on pneumococcal carriage was unknown in this setting. We assessed changes in pneumococcal carriage and antibiotic susceptibility in children aged <5 years (U5) and HIV-infected adults (HIV+ adults) post-PCV10 introduction.MethodsDuring 2009–2013, we performed annual cross-sectional pneumococcal carriage surveys in two sites with ongoing population-based surveillance: Kibera (U5 only) and Lwak (U5 and HIV+ adults, catch-up vaccination for children 1–4 years offered in 2011). Nasopharyngeal swabs (and oropharyngeal swabs in adults) were obtained for culture. Pneumococcal isolates were serotyped by multiplex PCR and Quellung. Antibiotic susceptibility was determined (2009 and 2013). We calculated changes in penicillin nonsusceptible (intermediate or resistant) pneumococci (PNSP) carriage by chi-squared test. Changes in PCV10-type (VT) pneumococcal carriage in 2013 compared with baseline (U5: 2009–10, adults: 2009 only) were calculated by modified Poisson regression by age and site.ResultsOverall, 2,962 U5 (2,073 in Kibera, 889 in Lwak) and 2,028 HIV+ adults were enrolled. VT carriage declined by 52–60% in children 1–4 years, by 60% in children <1 year in Kibera, and by 76% in HIV+ adults (table). PNSP carriage declined from 32.8% to 22.3% (P < 0.01) in HIV+ adults but did not change in U5 (Kibera: 77.0% vs. 75.5%, P =0.10; Lwak: 74.3% vs. 74.6%, P = 0.94).ConclusionThe infant PCV10 program was associated with declines in VT carriage among U5 and HIV+ adults, and declines in PNSP carriage among HIV+ adults; however, VT carriage remained >10% among U5 2 years post-PCV10 introduction.Table. PCV10-Type Carriage by Site and Age GroupsSiteKiberaLwakAge GroupYearCarriage (%)aPR (95% CI)*Carriage (%)aPR (95% CI)*<1 year2009–201038.2Ref.30.0Ref.201314.60.40 (0.26, 0.62)10.30.37 (0.11, 1.24)1–4 years2009–201038.6Ref.34.3Ref.201318.70.48 (0.37, 0.62)13.80.40 (0.27, 0.60)HIV+ adults2009——12.9Ref2013——2.80.24 (0.14, 0.41)aPR, adjusted prevalence ratio; CI, confidence interval.*Adjusted for respiratory illness ≤30 days, antibiotic use ≤7 days, and area used for cooking.Disclosures All authors: No reported disclosures.

A microsimulation model projecting the health care costs for resistance to antibacterial drugs in Sweden.

BackgroundPrevious studies have shown that increasing antibacterial resistance (ABR) globally will cause extensive morbidity, deaths and escalated health care costs.MethodsTo project economic consequences of resistance to antibacterial drugs for the Swedish health care sector, we used an individual-based microsimulation model, SESIM. Health care consumption was represented as increased numbers of hospital days, outpatient visits and contact tracing for individuals getting clinical infections or becoming asymptomatic carriers. The risk of contracting a resistant bacterium was calculated using the incidence of mandatorily notifiable ABR in Sweden.ResultsWe estimate accumulated additional health care costs attributable to notifiable ABR from 2018 until 2030 to EUR 406 million and EUR 1, 503 million until 2050. Until 2030 the largest proportion, more than EUR 247 million (EUR 958 million until 2050), was due to ESBL, followed by methicillin resistant Staphylococcus aureus, carbapenemase-producing Enterobacteriaceae, vancomycin-resistant Enterococci and penicillin non-susceptible Pneumococci which incurred costs of EUR 128 million (EUR 453 million, 2050), EUR 15 million (EUR 58 million, 2050), EUR 13 million (EUR 28 million, 2050) and EUR 2 million (EUR 6 million, 2050), respectively.ConclusionsProjections concerning the future costs of ABR can be used to guide priorities and distribution of limited health care resources. Our estimates imply that costs in Sweden will have doubled by 2030 and increased more than 4-fold by 2050 if present trends continue and infection control practices remain unchanged. Still, indirect societal costs and costs for non-notifiable resistance remain to be added.

Streptococcus pneumoniae: Antimicrobial Resistance and Serotypes of Strains Carried by Children and Causing Invasive Disease in the Faroe Islands.

Knowledge about pneumococcal carriage, antibacterial resistance, serotype prevalence, and prevalence of invasive pneumococcal disease (IPD) after introduction of pneumococcal conjugate vaccines (PCVs) is lacking in the Faroe Islands. PCV-7 was introduced in 2008 and PCV-13 in 2010. The aim was to obtain knowledge on serotypes and antimicrobial resistance in pneumococci from carriage in children attending day-care centers (DCCs) and invasive isolates. Nasopharyngeal swabs were collected from 607 healthy children attending DCCs in the Faroe Islands in January to March in 2009, 2010, and 2011. Pneumococci were cultured selectively, tested for antibacterial susceptibility, and serotyped. Data from IPD isolates from 1974 to 2016 from the Department of Microbiology, National Hospital of the Faroe Islands, and typed and stored at Staten Serum Institute were also analyzed. Of the 607 screened children, 45% were pneumococcal carriers, 50% in 2009, 40% in 2010, and 42% in 2011. Antibiotic resistance in pneumococci was rare both in carriers and patients. Five penicillin nonsusceptible pneumococci were found in carriers (1.8%) and one among the invasive isolates (1.7%). The most common serotypes in carriage were 6B and 6A in 2009, serotype 3 and 6C in 2010, and serotype 11 and 6C in 2011. Serotype 6B was not found in 2011. The most common serotypes among IPD were 7F and 3. Pneumococcal carriage prevalence in healthy children attending DCCs in the Faroe Islands was low and antibacterial resistance was rare, compared with Iceland. The results suggest a possible serotype shift, reduction in antibacterial use, and PCV-7/13 serotype decrease in IPD after the introduction of pneumococcal vaccinations in children.

Population structure of Streptococcus pneumoniae colonizing children before and after universal use of pneumococcal conjugate vaccines in Brazil: emergence and expansion of the MDR serotype 6C-CC386 lineage.

To determine the population structure and change in drug resistance of pneumococci colonizing children before and after the introduction of the 10-valent and 13-valent pneumococcal conjugate vaccines (PCV10/13) in Brazil. We used MLST to analyse 256 pneumococcal isolates obtained from children aged <6 years before (2009-10; n = 125) and after (2014; n = 131) the introduction of the PCV10 and PCV13. Antimicrobial susceptibility and capsular types were previously determined. We identified 97 different STs. Ninety (35.2%) isolates were related to international clones. The most frequent lineages were serogroup 6-CC724 (where CC stands for clonal complex) and the MDR serotype 6C-CC386 in the pre- and post-PCV10/13 periods, respectively. Penicillin-non-susceptible pneumococci (PNSP) formed 24% and 38.9% of the pre- and post-PCV10/13 isolates, respectively (P = 0.01). In the pre-PCV10/13 period, serotype 14-ST156 was the predominant penicillin-non-susceptible lineage, but it was not detected in the post-PCV10/13 period. Serotype 14-ST156 and serotype 19A-ST320 complex isolates had the highest penicillin and ceftriaxone MICs in the pre- and post-PCV10/13 periods, respectively. In turn, serotype 6C-CC386 comprised almost 30% of the PNSP and over 40% of the erythromycin-resistant isolates (MIC >256 mg/L) in the post-PCV10/13 period. Although PNSP strains were polyclonal, most resistant isolates belonged to a single genotype from each period. Higher erythromycin resistance prevalence (42%) in the post-PCV10/13 period was mainly attributed to MDR serotype 6C-CC386. Ongoing surveillance of pneumococcal clonal composition is important to evaluate PCV use outcomes and to identify factors other than PCVs that drive pneumococcal drug resistance evolution.

Pneumococcal carriage among children after four years of routine 10-valent pneumococcal conjugate vaccine use in Brazil: The emergence of multidrug resistant serotype 6C

BackgroundIn 2010, the 10-valent pneumococcal conjugate vaccine (PCV10) was introduced free of charge in Brazil as part of the public immunization program. Here we investigated the carriage prevalence, colonization risk factors, capsular types, and antimicrobial resistance among pneumococcal isolates obtained from children in Brazil four years after routine PCV10 use. MethodsBetween September and December 2014, we conducted a cross-sectional study among children<6years old who attended one public and two private clinics in Niterói, RJ, Brazil to evaluate pneumococcal nasopharyngeal carriage. Antimicrobial susceptibility and capsular types were determined for all isolates. ResultsOf 522 children, 118 (22.6%) were pneumococcal carriers. Being≥2years old, attending childcare center, presenting with any symptoms, having acute or chronic respiratory disease, and residing in a slum were associated with pneumococcal carriage. The most prevalent capsular types were 6C (14.5%), 15B/C (11.5%), 11A/D (9.2%), and 6A (7.6%). PCV10 serotypes represented 2.5%. All isolates were susceptible to levofloxacin, rifampicin, and vancomycin. Penicillin non-susceptible pneumococci (PNSP) comprised 39%, with penicillin and ceftriaxone MICs ranging from 0.12–8.0μg/ml and 0.012–1.0μg/ml, respectively. The 33 (28%) erythromycin-resistant isolates (MICs of 1.5 to >256μg/ml) displayed the cMLSB (72.7%) or M (27.3%) phenotypes, harboring the erm(B) and/or mef(A/E) genes. High non-susceptibility rates (>20%) to clindamycin, erythromycin, penicillin, and tetracycline were largely explained by the prevalence of multidrug resistant (MDR) serotype 6C isolates. ConclusionsEffects of universal childhood PCV10 use on carriage were evident, with the near elimination of PCV10 serotypes. The emergence of MDR serotype 6C isolates, however, is a concern. Ongoing surveillance to monitor serotype 6C increase in invasive diseases is warranted.

Streptococcus pneumoniae Serotypes 9 and 14 Circulating in Brazil over a 23-Year Period Prior to Introduction of the 10-Valent Pneumococcal Conjugate Vaccine: Role of International Clones in the Evolution of Antimicrobial Resistance and Description of a Novel Genotype

Antimicrobial-resistant pneumococcal strains have been detected worldwide since the 1960s. In Brazil, the first penicillin-nonsusceptible pneumococci (PNSP) were reported in the 1980s, and their emergence and dissemination have been mainly attributed to serogroup 9 and serotype 14 strains, especially those highly related to recognized international clones. In the present study, antimicrobial susceptibility testing and multilocus sequence typing were performed on 315 pneumococcal isolates belonging to serogroup 9 (n = 99) or serotype 14 (n = 216), recovered from patients or asymptomatic carriers between 1988 and 2011 in Brazil, in order to trace changes in antimicrobial resistance and genotypes prior to the full introduction of the pneumococcal conjugate vaccine in the country. Over the 23-year study period, the PNSP levels increased, and four clonal complexes (CC156, CC66, CC15, and CC5401) have played important roles in the evolution and dissemination of pneumococcal isolates belonging to serogroup 9 and serotype 14, as well as in the emergence of antimicrobial resistance, in the pre-pneumococcal-vaccination era. The earliest PNSP strains detected in this study belonged to serotype 9N/ST66 and were single locus variants of the international clone Tennessee14-18 ST67 (CC66). The first serotype 14 PNSP isolates were identified in 1990 and were related to the England14-9 ST9 (CC15) clone. Serotype 14 PNSP variants of the Spain9V-3 ST156 clone with elevated penicillin MICs and nonsusceptibility to other beta-lactams were detected in 1995 and showed an increasing trend over the years. The results also indicated that introduction of ST156 in our region was preceded by the emergence of trimethoprim-sulfamethoxazole resistance and by the dissemination of ST162. In addition to the presence of successful international clones, a novel regional serotype 14 genotype (CC5401) has emerged in 1996.

Long-term effects of penicillin resistance and fitness cost on pneumococcal transmission dynamics in a developed setting

BackgroundThe increasing prevalence of penicillin non-susceptible pneumococci (PNSP) throughout the world threatens successful treatment of infections caused by this important bacterial pathogen. The rate at which PNSP clones spread in the community is thought to mainly be determined by two key determinants; the volume of penicillin use and the magnitude of the fitness cost in the absence of treatment. The aim of the study was to determine the impacts of penicillin consumption and fitness cost on pneumococcal transmission dynamics in a developed country setting.MethodsAn individual-based network model based on real-life demographic data was constructed and applied in a developed country setting (Sweden). A population structure with transmission of carriage taking place within relevant mixing groups, i.e. families, day care groups, school classes, and other close contacts, was considered to properly assess the transmission dynamics for susceptible and PNSP clones. Several scenarios were simulated and model outcomes were statistically analysed.ResultsModel simulations predicted that with an outpatient penicillin use corresponding to the sales in Sweden 2010 (118 recipes per 1,000 inhabitants per year), the magnitude of a fitness cost for resistance must be at least 5% to offset the advantage of penicillin resistance. Moreover, even if there is a fitness cost associated with penicillin resistance, a considerable reduction of penicillin usage appears to be required to significantly decrease the incidence of PNSP in a community.ConclusionThe frequency of PNSP clones is hard to reverse by simply reducing the penicillin consumption even if there is a biological cost associated with resistance. However, because penicillin usage does promote further spread of PNSP clones, it is important to keep down penicillin consumption considering future resistance problems.

Temporal trends and clonal diversity of penicillin non-susceptible pneumococci from meningitis cases from 1996 to 2012, in Salvador, Brazil.

BackgroundHospital-based surveillance for pneumococcal meningitis has been conducted since January 1996 in the city of Salvador, Brazil. The purpose of this study was to describe the temporal evolution of Penicillin Non-Susceptible Streptococcus pneumoniae (PNSSP) in regards to serotype distributions and clonal diversity recovered from meningitis cases over 17 years.MethodsBroth microdilution was used to identify pneumococcal isolates that were PNSSP (Minimum Inhibitory Concentration > 0.12 μg/ml). The annual incidence rate of meningitis cases was calculated. Serotyping was defined using multiplex polymerase chain reaction assays and quellung reaction. Genetic diversity of PNSSP isolates was assessed using both pulsed-field gel electrophoresis (PFGE) and Multilocus Sequence Typing (MLST) analyses.ResultsA total of 854cerebrospinal fluid (CSF) culture pneumococcal isolates were tested by broth microdilution method and serotyped. A total of 173 (20.3 %) were penicillin non-susceptible (PNSSP) (Minimum Inhibitory concentration ≥ 0.12 μg/ml). The annual incidence of meningitis cases declined from 1.65/100,000 population (1996) to 0.2/100,000 population in 2012 and the rate due to PNSSP declined 82 % over the 17-years of surveillance. PNSSP isolates were restricted to 13 serotypes, being the most common ones serotypes14 (45.1 %; 78/173), 23 F (19.1 %; 33/173), 6B (14.4 %; 25/173), 19 F (9.2 %; 16/173) and 19A (5.2 %; 9/173). Among the PNSSP isolates, 94 % had serotypes represented in the 10-valent conjugate vaccine (PCV10). The predominant serotype 14 clonal groups were identified as PFGE group A/multilocus sequence type 66 (ST66) [35.3 % (61/173)] and PFGE group GK/ST156 [4.6 % (8/173)], the latter one associated with high level resistance to penicillin and ceftriaxone.ConclusionsOur results show sustained reductions in pneumococcal meningitis cases in the Metropolitan region of Salvador from 1996 to 2012. This might reflect a beneficial impact of conjugate vaccines. Continued surveillance and further studies need to be conducted to better understanding on PCV10 vaccine impact.

Prevalence of pilus genes in pneumococci isolated from healthy preschool children in Iceland: association with vaccine serotypes and antibiotic resistance.

The objective of this study was to investigate the prevalence of pilus islets [pilus islet 1 (PI-1) and pilus islet 2 (PI-2)] in pneumococcal isolates from healthy Icelandic preschool children attending day care centres, prior to the introduction of conjugated pneumococcal vaccine, and the association of the pilus islets with vaccine serotypes and antibiotic resistance. Nasopharyngeal swabs were collected from 516 healthy children attending day care centres in Reykjavik in March and April 2009. Infant vaccination was started in 2011, thus the great majority of the children were unvaccinated. Pneumococci were cultured selectively, tested for antimicrobial susceptibility and serotyped. The presence of PI-1 and PI-2 was detected using PCR. A total of 398 viable isolates were obtained of which 134 (33.7%) showed the presence of PI-1. PI-1-positive isolates were most often seen in serotype 19F [30/31 (96.8%)] and were of clade I, and in 6B [48/58 (82.8%)] of clade II. PI-2-positive isolates were most common in serotype 19F [27/31 (87.1%)]; all of them were also PI-1 positive. Of the PI-1-positive and PI-2-positive isolates, 118 (88.1%) and 31 (81.6%), respectively, were of vaccine serotypes. Both PI-1 and PI-2 were more often present in penicillin-non-susceptible pneumococci (PNSP) than in penicillin-susceptible pneumococci [PI-1 in 41/58 (70.7%) and 93/340 (27.4%), respectively, and PI-2 in 28/58 (48.3%) and 10/340 (2.9%), respectively]. Genes for PI-1 and/or PI-2 in pneumococci isolated from healthy Icelandic children are mainly found in isolates of vaccine serotypes and in PNSP isolates belonging to multiresistant international clones that have been endemic in the country.